Pharmaceutical Research

, Volume 29, Issue 1, pp 306–318 | Cite as

Extending Residence Time and Stability of Peptides by Protected Graft Copolymer (PGC) Excipient: GLP-1 Example

  • Gerardo M. CastilloEmail author
  • Sandra Reichstetter
  • Elijah M. BolotinEmail author
Research Paper



To determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes.


To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty acid at the epsilon amino groups. We performed evaluation of the binding of excipient to GLP-1, the DPP IV sensitivity of GLP-1 formulated with PGC as the excipient, the in vitro bio-activity of excipient-formulated GLP-1, the in vivo pharmacokinetics of excipient-formulated GLP-1, and the efficacy of the excipient-formulated GLP-1 in diabetic rats.


We showed reproducible synthesis of PGC excipient, high affinity binding of PGC to GLP-1, slowed protease degradation of excipient-formulated GLP-1, and that excipient-formulated GLP-1 induced calcium influx in INS cells. Excipient-formulated GLP-1 stays in the blood for at least 4 days. When excipient-formulated GLP-1 was given subcutaneously once a week to diabetic ZDF rats, a significant reduction of HbA1c compared to control was observed. The reduction is similar to diabetic ZDF rats given exendin twice a day.


PGC can be an ideal in vivo stabilizing excipient for biologically labile peptides.


diabetes glucagon like peptide peptide excipient protected graft copolymer 



dipeptidyl peptidase IV


Glucagon-like peptide-1


glycosylated hemoglobin


poly(ethylene glycol) conjugation


protected graft copolymer



This work was supported by the SBIR Grant #DK069727 from National Institute of Diabetes and Digestive and Kidney diseases of the National Institute of Health. The authors thank Ms. Cynthia Jones, Ms. Akiko Nishimoto-Ashfield, and Ms. Marisa Robinson for assistance with the manuscript.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.PharmaIN CorporationSeattleUSA

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